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Loss of adaptive capacity in asthmatics revealed by biomarker fluctuation dynamics upon experimental rhinovirus challenge

View ORCID ProfileAnirban Sinha, René Lutter, Binbin Xu, Tamara Dekker, Barbara Dierdorp, Peter J. Sterk, Urs Frey, Edgar Delgado-Eckert
doi: https://doi.org/10.1101/684910
Anirban Sinha
aAmsterdam UMC, University of Amsterdam, Department of Respiratory Medicine, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
bAmsterdam UMC, University of Amsterdam, Department of Experimental Immunology, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
cUniversity of Basel, University Children’s Hospital (UKBB), Spitalstrasse 33, Postfach, 4031 Basel, Switzerland
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  • ORCID record for Anirban Sinha
  • For correspondence: a.sinha@amc.uva.nl anirban.sinha@ukbb.ch
René Lutter
aAmsterdam UMC, University of Amsterdam, Department of Respiratory Medicine, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
bAmsterdam UMC, University of Amsterdam, Department of Experimental Immunology, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
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Binbin Xu
dUniversity of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, F-33000 Bordeaux, France
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Tamara Dekker
bAmsterdam UMC, University of Amsterdam, Department of Experimental Immunology, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
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Barbara Dierdorp
bAmsterdam UMC, University of Amsterdam, Department of Experimental Immunology, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
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Peter J. Sterk
aAmsterdam UMC, University of Amsterdam, Department of Respiratory Medicine, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
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Urs Frey
cUniversity of Basel, University Children’s Hospital (UKBB), Spitalstrasse 33, Postfach, 4031 Basel, Switzerland
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Edgar Delgado-Eckert
cUniversity of Basel, University Children’s Hospital (UKBB), Spitalstrasse 33, Postfach, 4031 Basel, Switzerland
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Abstract

Asthma is a dynamic disease, in which lung mechanical and inflammatory processes often interact in a complex, unpredictable manner. We hypothesize that this may be explained by respiratory disease-related systems instability and loss of adaptability to changing environmental conditions, resulting in highly fluctuating biomarkers and symptoms. Using time series of inflammatory (eosinophils, neutrophils, FeNO), clinical and lung function biomarkers (PEF, FVC, and FEV1), we estimated this loss of adaptive capacity (AC) during an experimental perturbation with a rhinovirus in 24 healthy and asthmatic volunteers. Loss of AC was estimated by comparing similarities between pre- and post-challenge time series. Unlike healthy participants, the asthmatic’s post-viral-challenge state resembled significantly more other rhinovirus-infected asthmatics than their own pre-viral-challenge state (hypergeometric-test: p=0.029). This reveals loss of AC, and supports the novel concept that not only single physiological mechanisms, but interacting dynamic disease properties are altered in asthma and contribute to a more vulnerable phenotype.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted July 02, 2019.
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Loss of adaptive capacity in asthmatics revealed by biomarker fluctuation dynamics upon experimental rhinovirus challenge
Anirban Sinha, René Lutter, Binbin Xu, Tamara Dekker, Barbara Dierdorp, Peter J. Sterk, Urs Frey, Edgar Delgado-Eckert
bioRxiv 684910; doi: https://doi.org/10.1101/684910
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Loss of adaptive capacity in asthmatics revealed by biomarker fluctuation dynamics upon experimental rhinovirus challenge
Anirban Sinha, René Lutter, Binbin Xu, Tamara Dekker, Barbara Dierdorp, Peter J. Sterk, Urs Frey, Edgar Delgado-Eckert
bioRxiv 684910; doi: https://doi.org/10.1101/684910

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